Akinetic mutism and gait disturbance in a patient with delayed post-hypoxic leukoencephalopathy.

We report on a patient with delayed post-hypoxic leukoencephalopathy (DPHL) who showed akinetic mutism and gait disturbance, neural injuries that were demonstrated on diffusion tensor tractography (DTT). A patient was exposed to carbon monoxide (CO) and rapidly recovered; however, two weeks after onset, he began to show cognitive impairment and gait disturbance. At six weeks after CO exposure, he showed akinetic mutism and gait inability. DTT at 6-weeks post-exposure showed discontinuations in neural connectivities of the caudate nucleus to the medial prefrontal and orbitofrontal cortex in both hemispheres. In addition, the corticoreticulospinal tract revealed severe thinning in both hemispheres.

Steroid-Responsive Encephalitis in Coronavirus Disease 2019.

Coronavirus disease 2019 (COVID-19) infection has the potential for targeting the central nervous system, and several neurological symptoms have been described in patients with severe respiratory distress. Here, we described the case of a 60-year-old patient with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection but only mild respiratory abnormalities who developed an akinetic mutism attributable to encephalitis. Magnetic resonance imaging was negative, whereas electroencephalography showed generalized theta slowing. Cerebrospinal fluid analyses during the acute stage were negative for SARS-CoV-2, positive for pleocytosis and hyperproteinorrachia, and showed increased interleukin-8 and tumor necrosis factor-α concentrations. Other infectious or autoimmune disorders were excluded. A progressive clinical improvement along with a reduction of cerebrospinal fluid parameters was observed after high-dose steroid treatment, thus arguing for an inflammatory-mediated brain involvement related to COVID-19. ANN NEUROL 2020;88:423-427.

Delayed post-hypoxic leucoencephalopathy presenting akinetic mutism after traumatic cervical cord injury: a case report.

Delayed post-hypoxic leucoencephalopathy is a demyelinating syndrome characterized by acute onset of neuropsychiatric symptoms including parkinsonism or akinetic mutism that occurs days to weeks after recovery from cerebral hypo-oxygenation. We encountered a patient who presented with an akinetic mute state late after cervical cord injury without a definite hypoxic event.

Vegetative state, minimally conscious state, akinetic mutism and Parkinsonism as a continuum of recovery from disorders of consciousness: an exploratory and preliminary study.

The aim of this study was to review the usefulness of clinical and instrumental evaluation in individuals with disorders of consciousness (DOC). Thirteen subjects with severe acquired brain injury (ABI) and a diagnosis of DOC were evaluated using the Coma Recovery Scale in its revised version (CRS-R) and a new global disability index, the Post-Coma Scale (PCS). These instruments were administered both by a neutral examiner (professional) and by a professional in the presence of a caregiver. All patients were also scored using the International Classification of Functioning, Disability and Health (ICF). A statistically significant correlation between CRS-R and PCS was demonstrated. However, there also emerged significant differences in responsiveness between professional versus caregiver+professional assessment using the two scales. The emotional stimulation provided by significant others (caregivers) during administration of DOC evaluation scales may improve the assessment of responsiveness.

On the pathophysiology and treatment of akinetic mutism.

Akinetic mutism (AM) is a rare neurological disorder characterized by the presence of an intact level of consciousness and sensorimotor capacity, but with a simultaneous decrease in goal-directed behavior and emotions. Patients are in a wakeful state of profound apathy, seemingly indifferent to pain, thirst, or hunger. It represents the far end within the spectrum of disorders of diminished motivation. In recent years, more has become known about the functional roles of neurocircuits and neurotransmitters associated with human motivational behavior. More specific, there is an increasing body of behavioral evidence that links specific damage of functional frontal-subcortical organization to the occurrence of distinct neurological deficits. In this review, we combine evidence from lesion studies and neurophysiological evidence in animals, imaging studies in humans, and clinical investigations in patients with AM to form an integrative theory of its pathophysiology. Moreover, the specific pharmacological interventions that have been used to treat AM and their rationales are reviewed, providing a comprehensive overview for use in clinical practice.

Akinetic mutism--not coma.

We describe a case of akinetic mutism mistaken as coma. A 77-year old lady presented with apparent unresponsiveness. In fact she responded when stimulated. She subsequently developed movements typical of clonic perseveration, erroneously treated as seizures. She also had features of a frontal lobe syndrome. Initial CT scan showed no abnormality; it was only after an MRI scan that a diagnosis of bilateral paramedian thalamic infarction was made. MRI scanning should be considered early in the investigation of patients with atypical neurological presentation.

Akinetic mutism and status epilepticus due to Epstein Barr virus encephalitis.

Neurological complications of Epstein Barr virus (EBV) infection are infrequent and may include occasionally encephalitis, usually with a benign evolution. We here report on an aggressive case of EBV encephalitis in a 14-year-old boy with extensive basal ganglia involvement, and to a lesser degree of brain cortex who presented atypically with akinetic mutism and non-convulsive status epilepticus, requiring intensive care but showed a favorable outcome. EBV encephalitis is uncommon and its best management is unclear. Its pathophysiology is not well understood but could include autoimmunity. Onconeuronal and synaptic antibodies were negative in serum and cerebrospinal fluid, including the dopamine D2 receptor. To the best of our knowledge, this is the first report to evaluate antibodies to D2 receptors in EBV encephalitis. Corticosteroid therapy is usually recommended but the use of acyclovir is controversial. Intensive care is required in severe cases to assure a favorable outcome.

Inflammatory cerebrospinal fluid in sporadic Creutzfeldt-Jakob disease.

BACKGROUND: Sporadic Creutzfeldt-Jakob disease (CJD) is a fatal, transmissible spongiform encephalopathy characterized by rapidly progressive dementia, myoclonus, ataxia and akinetic mutism. The underlying mechanism is believed to be a conformational change of a native prion protein which characteristically fails to provoke an immune response. Commensurate with the latter, cerebrospinal fluid (CSF) classically exhibits a non-inflammatory profile. CASES: We report two patients with pathologically-proven sporadic CJD presenting with a significant CSF pleocytosis. CONCLUSION: Although uncommon, the presence of an inflammatory CSF profile should not exclude the diagnosis of sporadic CJD.

Akinetic mutism following prefrontal injury by an electrical grinder a case report: A diffusion tensor tractography study.

RATIONALE: A 72-year-old male had suffered from head trauma resulting from injury to his frontal area by an electrical grinder while working at his home. PATIENT CONCERNS: He lost consciousness for approximately 10 minutes and experienced continuous post-traumatic amnesia. DIAGNOSES: He was diagnosed as traumatic intracerebral hemorrhage in both frontal lobes, intraventricular hemorrhage, and subarachnoid hemorrhage, and underwent decompressive craniectomy and hematoma removal. INTERVENTIONS: The patient's Glasgow Coma Scale score was 5. At 2 months after onset, when starting rehabilitation, he showed no spontaneous movement or speech; he remained in a lying position all day with no spontaneous activity. OUTCOMES: On 2-month diffusion tensor tractography, decreased neural connectivity of the caudate nucleus to the medial prefrontal cortex (PFC, Broadmann area [BA]: 10 and 12) and orbitofrontal cortex (BA 11 and 13) was observed in both hemispheres. LESSONS: Akinetic mutism following prefrontal injury.

Diminution of basal ganglia dopaminergic function may play an important role in the generation of akinetic mutism in a patient with anterior cerebral arterial infarct.

We report the clinical features and dopamine transporter [2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]amino]ethanethiolato(3-)-N2,N20,S2,S20]oxo-[1R-(exo-exo)]-[99mTc] technetium([99mTc]TRODAT-1) image finding in an 86-year-old woman with akinetic mutism due to infarction of bilateral anterior cerebral arterial territories. TRODAT-1 is a cocaine analogue that can be labeled with technetium-99m and bound to the dopamine transporter (DAT) site. It reflects primarily the integrity of presynaptic dopamine neuron terminals. With the evolution of the clinical features, the TRODAT SPECT images change from bilateral diminution of radioactivity uptake at the 81st-day check point to normal pattern at the 6-month one when the akinetic mute manifestations were nearly gone. This novel illustration suggests that the akinetic mutism caused by anterior cerebral arterial infarct is closely linked to the perturbation of the subcortical dopaminergic system. And the amelioration of the clinical features concordantly evolved with the restoration of the dopaminergic function.

Consciousness and altered consciousness.

The notion of consciousness in the English scientific literature denotes a global ability to consciously perform elementary and intellectual tasks, to reason, plan, judge and retrieve information as well as the awareness of these functions belonging to the self, that is, being self-aware. consciousness can also be defined as continuous awareness of the external and internal environment, of the past and the present. The meaning of consciousness is different in various languages, but it invariably includes, the conscious person is capable to learn, retrieve and use information. Disturbance or loss of consciousness in the Hungarian medical language indicates decreased alertness or arousability rather than the impairment of the complex mental ability. Awareness denotes the spiritual process of perception and analysis of stimuli from the inner and external world. Alertness is a prerequisite of awareness. Clinical observations suggest that the lesions of specific structures of the brain may lead to specific malfunction of consciousness, therefore, consciousness must be the product of neural activity. "Higher functions" of human mental ability have been ascribed to the prefrontal and parietal association cortices. The paleocerebrum, limbic system and their connections have been considered to be the center of emotions, feelings, attention, motivation and autonomic functions. Recent evidence indicates that these phylogenetically ancient structures play an important role in the processes of acquiring, storing and retrieving information. The hippocampus has a key role in regulating memory, learning, emotion and motivation. Impaired consciousness in the neurological practice is classified based on tests for conscious behavior and by analyzing the following responses: 1. elementary reactions to sensory stimuli--these are impaired in hypnoid unconsciousness, 2. intellectual reactions to cognitive stimuli--these indicate the impairment of cognitive contents in non-hypnoid unconsciousness. Obviously, disturbance of elementary reactions related to alertness and disturbance of intellectual performance overlap. In conditions with reduced ability to react to or to perceive external stimuli the cognitive disturbance of consciousness cannot fully be explored.

Quadrigeminal cistern lipoma.

Intracranial lipomas are rare benign congenital neoplasms accounting for 0.1 to 0.5% of all primary brain tumours. Approximately 50% are associated with other cerebral developmental disorders. These slow growing benign lesions are usually asymptomatic and rarely require surgery. We report the case of a 37 year old woman presented with signs of raised intracranial pressure. Computerized tomography and magnetic resonance imaging demonstrated a quadrigeminal cistern lipoma compressing the aqueduct of Sylvius. The patient underwent surgery and a distinct plane of cleavage between the lipoma and the adjacent neural structures was found, allowing total removal of the lesion. Postoperatively, the patient was relieved of her original symptoms but developed akinetic mutism which lasted for two weeks. Intracranial lipomas rarely become symptomatic and surgery is seldom required. If the lesion progresses and causes symptoms of raised intracranial pressure or compression of neural structures, surgical intervention is indicated. Total removal should not be attempted unless a plain of cleavage between the lesion and adjacent neural structures is present. Surgical manipulation should be minimised to avoid complications.

Sleep abnormalities in patients with brain stem lesions.

Seven patients with "locked-in" syndrome were studied by prolonged polygraphic recordings. Severe alterations in the sleep pattern were observed in five patients who had bilateral extensive pontine lesions resulting in tetraplegia, facial and pseudobulbar paralysis, and absence of conjugate horizontal gaze. Rapid eye movement (REM) sleep was entirely absent while non-rapid eye movement (NREM) sleep was absent, reduced, or altered. The remaining two patients, both of whom had relative sparing of horizontal gaze and apparently either no or minimal pontine tegmental involvement, showed both REM and NREM sleep with only a minimal alteration in the sleep pattern. The study suggests that, in human beings as in animals, pontine structures near the midline are essential for control of sleep states.

OKT3 neurotoxicity presenting as akinetic mutism.

BACKGROUND: Muromonab-CD3 (OKT3), a mouse monoclonal antibody directed against human T lymphocytes, is a potent immunosuppressive agent used to reverse and more recently to prevent allograft rejection, mostly in cardiac transplant recipients. Neurotoxicity from OKT3 usually manifests itself as a transient aseptic meningitis and remains uncommon. METHODS: The authors describe a dramatic neurologic syndrome after orthotopic heart transplant characterized by akinetic mutism, blepharospasm, anomic aphasia, and delirium. RESULTS: Magnetic resonance imaging (MRI) showed meningeal enhancement and single-photon emission computed tomography (SPECT) showed markedly reduced tracer uptake. Discontinuation of OKT3 resulted in resolution of this neuropsychiatric syndrome and reversal of abnormalities on neuroimaging that coincided with normalization of CD3+ lymphocyte count. CONCLUSIONS: In the initial posttransplant period, it remains difficult to attribute encephalopathic signs to toxicity of immunosuppressive drugs. However, MRI and cerebral perfusion studies may help support the diagnosis. More precise characterization of the prevalence of OKT3-associated encephalopathy could come from prospective SPECT studies.

Preserved auditory cognitive ERPs in severe akinetic mutism: a case report.

kinetic mustism is a dramatic deficit in spontaneous initiation of voluntary motor and speech acts, usually secondary to bilateral lesions of the anterior cingulate cortices and supplementary motor areas [Principles of Neurology, McGraw-Hill, New York, 1989]. Given the obvious limitations of traditional neuropsychological testing in this clinical context, the use of neurophysiological tools such as bedside auditory cognitive event-related potentials (ERPs), recently proven to be relevant to evaluate comatose and vegetative patients [Clin. Neurophysiol. 110 (9) (1999) 1601; News Physiol. Sci. 17 (2002) 38], may constitute an interesting alternative. Here, we present the ERPs of a 38-year-old right-handed woman with severe akinetic mutism recorded in a passive auditory odd-ball paradigm. In spite of this severe clinical state, we could observe the presence of a "Mismatch Negativity", and of a larger P300 in rare trials than in frequent ones. By revealing a high level of cognitive integration of environmental auditory information, our study emphasizes the potential clinical relevance of MMN and P300 recordings in akinetic mutism to assess patient cognitive functioning.

Chronic akinetic mutism after mesencephalic-diencephalic infarction: remediated with dopaminergic medications.

OBJECTIVE: Akinetic mutism (AKM) is an uncommon disorder with a complex neuropathology. There is no generally accepted treatment, and it is not known if late treatments are effective. The relationship between AKM and abulia is uncertain. METHODS: The effects of dopaminergic treatment of a patient with chronic AKM after discrete bilateral infarctions of the mesencephalic ventral tegmental area and the lateral hypothalamus were studied with motor measures, the Functional Independence Measure (FIM), and neuropsychological tests. RESULTS: Treatment with a combination of carbidopa/levodopa and pergolide produced prompt amelioration of AKM with dramatic and rapid improvement in FIM. An apathetic, amotivational state persisted despite resolution of akinesia and normal frontal executive functions. CONCLUSIONS: AKM may respond to dopaminergic treatment even after months of severe akinesia. The mechanism of abulia is more complex than simply a partial dopaminergic deficiency state and may persist even when AKM is treated and frontal cognitive functions are normal.

Akinetic mutism in bilateral necrotizing leucoencephalopathy after radiation and chemotherapy: electrophysiological and autopsy findings.

In a patient with akinetic mutism, extensive circumscribed bilateral lesions in the precentral part of the centrum semiovale, due to delayed necrotizing leucoencephalopathy after combined intravenous polychemotherapy and radiation, were found at autopsy. CT and somatosensory evoked potentials were normal and a slow alpha rhythm was present, but there was a lack of EEG desynchronization. Akinetic mutism and the loss of desynchronization in this case are thought to result from interrupted thalamofrontal and extrathalamic reticulofrontal projections and the disconnection of the anterior limbic cortex.